FACULTY:

FACULTY DISCLOSURE STATEMENTS:

Dr. Andrea F. Fus has no actual or potential conflicts of interest in relation to this activity.

Postgraduate Healthcare Education, LLC does not view the existence of relationships
as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically
rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

ACCREDITATION STATEMENT:

PharmacyPostgraduate Healthcare Education, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.UAN: 0430-0000-11-025-H01-PCredits: 2.0 hours (0.20 ceu)Type of Activity: Knowledge

TARGET AUDIENCE:

This accredited activity is targeted to pharmacists. Estimated time to complete this activity is 120 minutes.

DISCLAIMER:

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information
presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment
discussed or suggested in this activity should not be used by clinicians without evaluation of their patients' conditions and possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.

GOAL:

To educate community pharmacists about healthy iodine nutritional status and risk factors for deficiency.

OBJECTIVES:

After completing this activity, the participant should be able to:

Describe the role of dietary iodine.

Specify risk factors for iodine deficiency disorders.

Discuss the status of iodine sufficiency in the U.S., sources of dietary and nondietary iodine, and whether dietary sodium reduction will affect iodine intake in Americans.

Explain the pharmacist's role in educating the public about preventing iodine deficiency.

Iodine is an essential element for normal mammalian development and
function. Although iodine
deficiency disorders (IDDs) are less prevalent in the
United States, they are a
common problem in many
countries. Iodine deficiency
is a leading cause of preventable childhood brain damage and a serious public
health problem. Because salt (sodium chloride) is consumed in most diets and is relatively inexpensive to
fortify with iodine, universal salt iodization (USI) programs are embraced by most countries. Efforts to prevent
iodine deficiency through USI are being made concurrently with campaigns to reduce added sodium in our
food, as excessive sodium intake is associated with a risk
of cardiovascular and other morbidities. While reducing
the salt added to foods is not expected to impact global
efforts toward iodine fortification of populations, it may
be necessary to educate pregnant women and parents of
young children to ensure adequate iodine consumption
through improved food choices
(including selection of iodized salt
for home food preparation) or supplements. Pharmacists answer many
questions about iodine consumption
and the iodine content of
medicines, supplements,
foods, and other sources,
and they can recommend
steps for maintaining a
healthy iodine level.

Extensive research about
negative cardiovascular and
other health effects of excessive dietary sodium intake
has prompted recommendations by the Institute of
Medicine of the National Academies to broadly reduce
sodium content in the U.S. food supply.1 Sodium chloride, or common salt, is the primary source of sodium
in the U.S. diet. Daily, the average American consumes
more than 3,400 mg of sodium, which equals about 8.5
g (1.5 tsp) of salt.2 The 2010 U.S. Dietary Guidelines
for Americans developed by the Department of Agriculture and the Department of Health and Human Services
recommend a maximum daily intake of 2,300 mg of
sodium (5.8 g of salt) and further advise that specific
subpopulations amounting to about half of the U.S.
population should reduce daily intake to 1,500 mg.

Concerns have been raised that the
general reduction of sodium, primarily through foods with added salt,
could have unintended effects. The
most sustainable long-term strategy to control iodine deficiency and resultant disorders is to
fortify food. Iodized salt is preferred because of its ubiquitous nature and low cost. Issues that impact healthy
nutritional iodine status, including dietary sodium reduction, are discussed below.

An Essential Element

The element iodine exists naturally as a gas, and the solid
form can sublime without melting.3 Iodine is widely and
irregularly distributed in the environment, mainly in
ocean water and generally as iodide. Environmental iodine
fluctuates by means of atmospheric-terrestrial-aquatic
interactions.4 Iodine cycling occurs when oxidation of
seawater iodide salts releases iodine into the atmosphere,
after which precipitation returns the element to earth
surfaces. Iodine and other substances in soil and groundwater are subsequently incorporated into food and water.
Depletion of iodine in the earth’s soil occurs through
glacier melts, floods, erosion, and other influences.

The term iodine is used to refer to the element itself,
as well as to its salts. Iodine is present in foods as inorganic iodine, iodide, or iodate. Iodide is well absorbed
in the stomach and small intestine, whereas iodate is
reduced in the gastrointestinal tract and absorbed as
iodide. Absorbed iodine is concentrated in vertebrates’
thyroid gland and is used to synthesize the thyroid hormones thyroxine and triiodothyronine.5 These hormones
regulate metabolic and enzymatic processes, affecting the
development and function of the brain, muscle tissues,
pituitary gland, kidney, and nearly all other cells. Excess
iodine is excreted in the urine.

In addition to its nutrient functions, iodine is an
antimicrobial agent in certain surface disinfectants for
human and animal use. Iodine salts can be protective,
as in the case of perchlorate exposure or as demonstrated
after the Chernobyl nuclear reactor radiation emergency
in 1986.6 While iodized table salt is not indicated for
radiation protection, it became a scarce commodity in
Japan when the recent earthquake and tsunami caused
panic about a potential nuclear crisis at the Fukushima
Daiichi plant.7

The body cannot synthesize iodine, so this trace element must be obtained through the diet. Populations
living in areas with poor access to marine-derived foods,
whose drinking water has a low iodine content, or whose
diet primarily contains foods grown in iodine-deficient
soils are at risk for developing iodine deficiency. This
was evidenced by a relatively high prevalence of goiter
(an often noticeably enlarged thyroid) in the inland
intermountain, Midwestern, and Great Lakes areas of
the U.S. in the early 1900s, leading to the region being
termed the “goiter belt.”8,9

The association between goiter and environmental
iodine deficiency has since been questioned.10 The effects
of iodine deficiency on the development of goiter and
thyroid function vary between individuals and population
groups and are influenced by dietary, environmental, and
genetic factors.8

Regardless of its precise origin, goiter associated with
iodine deficiency is common globally and often can be
corrected if treated in time.8,9 Conversely, cretinism—a
severe irreversible condition of diminished physical and
mental growth following maternal and fetal iodine deficiency—is uncommon in the U.S. and other developed
countries. Goiter and cretinism, along with hypothyroidism, test scores indicating low cognitive ability, and other
developmental and growth disorders, are termed IDDs.
Americans are among the highest users of iodized salt
and constitute the group with least insufficient iodine
intake.9 However, data from 1994 to 2006 suggest that
almost 2 billion people, or about one-third of the world
population, are iodine deficient, including 98 million
individuals in the Americas.9 While severe iodine deficiency is uncommon in the U.S., there is concern for
some subgroups of reproductive-age women who do not
consume dairy products.11 Iodine deficiency is the main
cause of preventable childhood brain damage and a major
public health problem throughout the world, including
areas or groups in developed countries.

The World Health Organization (WHO) recommends
USI to prevent and treat IDD. The WHO advocates
individualized regional programs based on factors such
as population urinary iodine status, goiter prevalence,
and mean dietary salt intake.8 Excessive iodine can lead
to abnormal thyroid and metabolic activity and is associated with hypothyroidism and autoimmune thyroiditis.12 Hypothyroid and other individuals can be hypersensitive
to the actions of an extraphysiological supply of iodine.13 Coexisting deficiencies of selenium, iron, and vitamin A
can exacerbate the effects of iodine deficiency.14,15

Intervention

After research demonstrated a benefit from iodine supplementation, Switzerland and the U.S. were the first countries to establish population iodine supplementation
through salt fortification.16 The Akron Experiment was
an important study in the early 20th century that evaluated the effects of iodine supplementation in more than
4,000 girls in grades 5 and above.17 Girls with parental
consent to participate received water with sodium iodide
on 10 consecutive schooldays every 6 months for 2.5
years. Girls whose parents did not consent served as
controls. In girls with enlarged thyroid at baseline, 60.3%
of those receiving iodine had a smaller thyroid, compared with 13.8% of controls. For girls with normal thyroid
size at baseline, enlargement occurred in 0.2% of those
treated with iodine versus 27.6% of controls.

Based on these results, iodized salt was first sold commercially in grocery stores in 1924, and all salt used for
food, manufactured, or brought into Michigan State
contained iodine.17,18 Iodized salt was quickly adopted,
and large distributors sold the new product nationally.
Originally, potassium iodide was added to U.S. table salt
in an amount based on an average dietary sodium intake
of 6.5 g per day.16 (Interestingly, this average was determined by a Michigan physician, David Murray Cowie,
upon observing his family’s intake.) The intent was to
provide a conservative excess of dietary iodine compared
with the then-required range.

In the 1920s, most food consumed by Americans was
homemade, and means of distributing certain foods rich
in iodine, such as ocean foods, were limited. Salts were
used to cure or dehydrate foods to prevent spoilage. Also
at that time, it was realized that sodium nitrite (saltpeter)
not only preserved food and the red color of meat, but
inhibited Clostridium botulinum.19 Consistent with Dr.
Cowie’s observations, dietary sodium—although at higher
levels than those recommended now—was mostly consumed in foods prepared at home or added at the table.
The contribution of dietary iodine intake from iodized
salt has varied over time, and it has trended downward
as packaged foods, which typically do not contain iodized
salt, have increasingly replaced many meals and snacks
formerly prepared at home. Indeed, only about 5% of
average U.S. dietary sodium intake is added by the
consumer as table salt, and the Salt Institute, a nongovernmental organization, estimates that only about 70%
of households use iodized salt.20,21 On average, based on
a dietary sodium intake of 3,400 mg, iodized salt probably accounts for only 3.5% of the daily sodium intake
of most Americans.

USI was embraced by the World Health Assembly
almost two decades ago.22 Iodization of salt for both
human and livestock consumption was based on assumptions about average dietary salt intake and potential
iodine losses before product consumption. Worldwide
iodine-fortification programs are tailored to address the
extent of regional iodine deficiency, estimated iodine
losses, and factors such as deficiency of other dietary
microelements or consumption of goitrogenic foods.22,23

A panel of experts representing the International
Council for the Control of Iodine Deficiency Disorders,
the U.S. Agency for International Development, Health
Canada, the Pan American Health Organization, the
FDA, and the International Life Sciences Institute affirmed
the compatibility of the global campaign to iodize salt
with concomitant efforts in many countries to lower
sodium intake to moderate levels.24

Regulation

The use and availability of iodized salt in the U.S. are
voluntary, and the use of iodized salt has practically
eliminated goiter. Chemical forms of an iodide or iodate
of potassium, copper, calcium, or sodium are used when
iodine is added to foods.25 Potassium iodide is not stable,
and moisture, light, heat, and other environmental conditions reduce the available iodine content.4,26

Potassium iodide and cuprous iodide are considered
Generally Recognized as Safe (GRAS) for iodine fortification of salt in the U.S., whereas potassium and calcium
iodate are listed as food additives for technical effects in
dough.25 Manufacturers add potassium iodide to table
salt by spraying it onto the salt as it passes on a conveyor
belt or by mixing the dry powder with salt crystals at
concentrations from 0.006% to the regulatory limit of
0.01%, which is equivalent to 0.0046% to 0.0077% (77
mcg/1 g, or just under one-fourth tsp of iodized table
salt) iodine.27,28 Additionally, food-grade salt usually is
not pure sodium chloride. Salt is a hygroscopic crystalline
product, and humid storage conditions can cause the
crystals to clump. Voluntary standards allow up to 2%
(total) of suitable food-grade anticaking or conditioning
agents such as calcium silicate, sodium thiosulfate, dextrose, sodium bicarbonate, sodium carbonate, or sodium
thiosulfate to be added—singly or in combination—to
improve product flow, increase alkalinity, stabilize the
potassium iodide, and reduce oxidation and volatilization
of iodine from the product.29 Potassium iodate, which
is more stable, is one of 10 sources of iodine listed for
use in U.S. animal feed, but it is not explicitly identified
as GRAS for general human food use.29 U.S. food manufacturers are not required to list iodine content on food
labels unless the food has been fortified. The amount of
iodine in infant formula must be stated and must be
between 5 mcg and 75 mcg per 100 kcal of formula as
prepared for consumption.

Iodine fortification of foods is mandatory in many
countries. Australia and New Zealand have required
manufacturers to use iodized salt in bread manufacturing
since 2009.13 Iodization of table salt was made mandatory
in Canada in 1949 (with the exception of specialty salts).30

Recommended Intakes

A variety of Dietary Reference Intakes (DRIs) are used
by governments and interest groups to estimate the dietary
adequacy of iodine.9,31 Estimated Average Requirements
(EARs) meet the requirements of about half of the U.S.
population in a particular life stage and are used as a reference intake recommendation to establish Recommended Dietary Allowances (RDAs). For iodine, recommendations are estimated based on thyroid iodine accumulation and turnover in euthyroid subjects with adequate
iodine status. RDAs for iodine are based on the EAR,
such that intake meets the requirements of about 97%
to 98% of individuals in various life stages. Adequate
Intakes (AIs) are set when there is insufficient evidence
to determine an EAR. For iodine, the AI is set at 95
mcg/person/day, which is the AI for all children and for
all adults who are not pregnant or lactating.

The most recent DRIs for iodine, which were set by
the National Academies in 2001, are summarized in TABLE 1.31 The RDA for adult men and women is 150
mcg/day. However, the recommended intake for iodine
during pregnancy is 220 mcg/day and during lactation
is 290 mcg/day, and the 2001 Micronutrients Report
workshop panel recommended further research on iodine
requirements for lactating women.32 A Tolerable Upper
Intake Level (UL) is determined for nutrients that may
have harmful effects when consumed in excessive amounts.
The UL for iodine is estimated as the highest value that
is not likely to cause adverse health effects in most
individuals in a population. The UL for iodine for
adults is 1,100 mcg/day, which is based on serum thyrotropin concentration in response to varying levels of
ingested iodine.

Iodine Sources

Much of the iodine in today’s diet comes from nonsalt
sources in processed foods, such as iodine-containing
food additives, processing aids, and foods grown in
iodine-rich soil. The iodine content of foods can vary
tremendously. Seaweed, such as the nori sheets used to
make certain types of sushi, may have very high levels
of iodine. Finfish, shellfish, crustaceans, and sea-based
additives, including carrageenan, agar-agar, algin, and
alginate, contain iodine. Dairy products, particularly
milk, yogurt, eggs, and some cheeses, have moderate
amounts of iodine. Iodates have been used as dough
conditioners in enriched breads and as additives in macaroni products; however, many manufacturers now use
noniodine-containing additives. Some food sources of
iodine and their approximate iodine content are listed
in TABLE 2.33

In a survey of the iodine content of bread, milk, and
infant formula, 20 breads sampled in the U.S. from
2001 to 2002 had an iodine content ranging from 2.2
mcg to 587 mcg per slice (weight per slice ranged from
25.3-51.2 g, with one outlier of 13.9 mcg iodine in a
132.1-g sample).34 Iodized salt was not listed on any
package as an ingredient. Some packages listed iodated
dough conditioners, but their presence in the formula
did not always correlate with the measured iodine
content. The iodine content of 18 samples of cow’s
milk and infant formula had a tighter range: 88 mcg
to 168 mcg per 250 mL. The iodine content in eight
different infant formulas ranged from 16.2 mcg to 56.8
mcg per 148 mL.

Significant losses of naturally occurring iodine or
iodine-containing food additives may be caused by environmental factors in transportation and storage by the
producer and consumer, and also by processing and
cooking. An analysis of the effects of cooking on the
iodine content of fish found that boiling, grilling, or
frying haddock fillets resulted in iodine losses of 58%,
23%, and 20%, respectively.35 The amount of iodine in
cow’s milk has been linked to the amount of iodine
supplemented in the cows’ diet.36 Iodine is present, but
at lower concentrations, in the skeletal muscle of farm
animals given iodine-fortified feed or salt licks as a component of their diet.

Estimating Nutritional Iodine Status

Urinary Iodine:Because the iodine content of food
products can vary greatly and about 90% of iodine is
excreted in the urine, urinary iodine (UI) concentration,
rather than dietary intake, is used to monitor nutritional
iodine status. UI is often expressed as micrograms
(excreted per day), and spot urine samples are often
used for population estimates. A median value, rather
than a mean, is used for interpretation because UI
values are not normally distributed.37 The WHO assesses
sustainable IDD elimination by surveying children aged
6 to 12 years, a close age group with available data, or
specific population groups. The WHO advises that no
more than half of a population fall below a UI of 100 mcg/L; that a median UI of 100 mcg to 199 mcg/L
for a general population indicates sufficient nutritional
iodine status; and that the median in pregnant women
is 150 mcg/L to 249 mcg/L.8 Low population UI values suggest an overall risk for developing thyroid disorders and are considered with other factors, such as
goiter rate, neonatal serum thyroid-stimulating hormone,
and serum thyroglobulin.

The median UI concentration for the general U.S.
population in the early 1970s was estimated to be 320
mcg/L, suggesting excessive iodine intake.38 Concerns
about the use of iodophor cleaning agents in dairy-product production, high levels of iodine in animal
feed, red dyes containing iodine, and iodate baking
conditioners in breads led to decreased use.39 The median
UI concentration reported by the National Health and
Nutrition Examination Survey (NHANES) for 2005
through 2008 was 164 mcg/L, which is considered
optimal.40

Iodine Intake:The Total Diet Study (TDS) has determined levels of various contaminants and nutrients in
foods for over 50 years, and it is one of the few sources
of information on nutritional iodine status in the American diet. Analysis of iodine in food as prepared for
eating (e.g., a peeled banana) has been included since
2003. The TDS reports annual information for more
than 280 foods and beverages that has been aggregated
from 6,000 survey foods and beverages sampled from
four regions of the country. Iodine was detectable in at
least one sample in 59% of TDS foods and was undetected in the remaining 41%.41

Based on TDS food data and consumption data from
the NHANES for 2003 through 2004, the estimated
average iodine intake by males and females aged 2 to 74
years in 14 life-stage groups ranged from 138 mcg to
353 mcg (values adjusted for uncertainty in detection).41 These levels exceed estimated requirements for children
and nonpregnant and nonlactating adults. However, the average daily intake for women of reproductive age in
the TDS (14-16 years and 25-45 years) was 178 mcg to
214 mcg and 145 mcg to 197 mcg, respectively, revealing that many females in these populations would need
iodine supplementation if they became pregnant or started
lactating and did not change their diet. The TDS does
not include iodine intake from iodized salt added by the
consumer, tap water, or dietary supplements.

Although the iodine content of prenatal vitamins is
unregulated, the American Thyroid Association recommends that pregnant and lactating women receive prenatal vitamins containing 150 mcg of iodine.42 Of 19 supplements listed specifically for prenatal use in the 2006 Physicians’ Desk Reference, only one contained 150
mcg of iodine; the others did not list any iodine content.
Alarmingly, a more recent analysis of 223 prescription
and nonprescription prenatal vitamins showed that 49%
did not contain iodine.43 For products with labeling
stating that they contained 150 mcg per daily dose, the
measured iodine ranged from 33 mcg to 610 mcg per
daily dose. Pharmacists may guide both prescribers and
patients in choosing products that help pregnant women
meet their overall iodine intake goals.

Dairy products make the greatest contribution to daily
iodine intake in males and females older than 14 years,
ranging from 45% to 63%; grains contribute 16% to
23%.41 Mixed meals contribute 5% to 8% of iodine
intake for any age/sex group, and egg, meat, poultry, and
fish contribute 5% or less. Dairy products contribute
about 70% of the total estimated daily intake of iodine
in children aged 2 to 6 years. When asked to recommend
vitamins for children, the pharmacist should ask whether
the child consumes a vegan or low- or no-dairy diet and
should probe to determine whether the selection of a
vitamin with iodine is appropriate.

It is not possible to estimate the contribution of
iodized salt that is not consumed at home and added
while cooking or at the table. Food manufactured for
individual sale in the U.S. must list ingredients on the
label; this can assist in determining whether a particular brand of bread contains iodine as an additive. While
there is no single database of all packaged food labels
marketed in the U.S. at any given time, an analysis of
228,895 new variants of food and drink products
introduced between June 1996 and April 2011 and
tracked by Mintel International’s Global New Products
Database listed iodine from any source in 1,034 (0.45%)
new product variants, and 916 products (0.40%) listed
iodized salt on the ingredient label.44 While the database
captures label information only from new product
introductions, these data corroborate findings that
iodized salt is not a major source of dietary iodine intake
from packaged foods, which make up the majority of
the average American diet.

There is no standard method of determining whether
restaurants use iodized salt. Bulk packages of food-grade
iodized salt are available in the U.S., and this salt may
be used in packaged or restaurant food or for filling salt
shakers at food establishments. It is believed that noniodized salt is used by most food-processing manufacturers and food-service providers.26

Iodine from nonfood sources and unintentional iodine
residues can contribute to iodine intake status. Nonfood
sources of iodine include cosmetics, vitamins, supplements,
medication, and external disinfectants. Some of these
products can be a concern for individuals prescribed a
restricted iodine diet prior to certain medical procedures,
but they are not part of usual estimates of iodine intake.
Erythrosine (FD&C Red No. 3, which contains four
iodine molecules) has been banned for use generally except
as a straight color in foods and dietary supplements.45 Medical products containing iodine include water-purification tablets, radiographic contrast media, medicines such
as amiodarone (Cordarone) and some red- and pink-colored oral solutions, and iodophor dermal disinfectants
such as povidone-iodine. Povidone-iodine is a stable chemical complex of polyvinylpyrrolidone (povidone) and
elemental iodine that contains 9% to 12% iodine. Common names of medications containing iodine include
tincture of iodine, Lugol’s solution, and Betadine. Iodophor
preparations are also used by brewers, winemakers, and
the dairy industry to sanitize bottles and equipment.46

Conclusion

The introduction of iodized table salt has dramatically
reduced the incidence of goiter in the U.S. compared
with a century ago. Since that time, the availability of
foods prepared outside the home and the American
lifestyle have undergone major changes. Decades of
evidence have linked excessive dietary sodium consumption with cardiovascular risk, and most sodium in the
American diet comes from sodium chloride. Because the
average person’s diet consists primarily of packaged and
prepared foods, reducing sodium in the U.S. food supply
is considered a primary strategy to reduce excessive consumption. The contribution of iodized salt to the average
dietary sodium intake is small, and sodium reduction in
packaged and prepared foods would not be expected to
change the population’s iodine status. Some individuals,
including pregnant and lactating women, may be at risk
for iodine deficiency and can benefit from education by
pharmacists regarding a diet that includes foods or supplements containing sufficient iodine or the selection of
iodized salt for home use.

World Health Organization, International Council for Control of Iodine
Deficiency Disorders, United Nations Children’s Fund. Assessment of Iodine
Deficiency Disorders and Monitoring Their Elimination.AGuide for Programme
Managers. 3rd ed. Geneva, Switzerland: World Health Organization; 2007.

International Council for the Control of Iodine Deficiency Disorders.
PAHO panel declares no conflict between salt iodization imperative and salt
reduction efforts. www.iccidd.org/pages/posts/paho-panel-declares-no-conflictbetween-salt-iodization-imperative-and-salt-reduction-efforts161.php. Accessed May 25, 2011.

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